APPLICANT'S ABSTRACT: Alcohol abuse and dependence and nicotine dependence are major health problems in the U.S. Each is exacerbated when used together. Combined pharmacotherapies may offer promising new directions for treating dually-dependent patients. Specifically, transdermal nicotine replacement (TNR) and naltrexone (NTX) have significant clinical utility for the treatment of smoking and alcoholism, respectively. These medications, when used simultaneously, may facilitate smoking cessation during alcohol treatment. Such medication effects would be optimized in the context of adjuvant psychotherapeutic interventions, particularly those emphasizing relapse prevention (RP) skills training. It is our contention, that the concurrent application of TNR and NTX has a definite role within the context of nicotine-alcohol treatment and that there is a pressing need for a prospective clinical trial. The proposed double-blind, placebo controlled, 2x2 factorial study will determine the potential interactions between the two treatments by crossing alcohol treatment (NTX 50mg/d vs. placebo) with smoking treatment (active TNR vs. placebo). Both pharmacotherapies will be applied within a context of a cognitive-behavioral RP skills training therapy that emphasizes the linkage between smoking and drinking. Alcohol-nicotine dependent subjects (n=200) will be randomly assigned to one of four outpatient treatment conditions, then begin the 12-week trial involving weekly clinic visits. Smoking status will be based on self-report, expired air carbon monoxide and saliva cotinine levels. Alcohol consumption will be measured by self-report, breath alcohol readings, collateral reports, and liver function tests. Primary efficacy parameters for drinking and smoking will include time to lapse/relapse and cumulative absence duration. Secondary efficacy measures will include alcohol and smoking consumption, clinical global impression, retention in treatment, ASI scores, and medication compliance. We predict that subjects receiving TNR and NTX as adjuncts to RP will have higher rates of abstinence from both substances than subjects who do not receive these pharmacologic adjuncts. Secondary aims of this study will include: 1) assess the influences of process variables (coping, self-efficacy, craving, depression) on treatment outcome; 2) test the prognostic significance of patient variables (nicotine/alcohol dependence, readiness to change, stress, depression), as well as explore potential patient-treatment matching effects; 3) evaluate the maintenance of treatment gains over a 6-month follow-up period. The results will advance our understanding of clinical research issues related to the concurrent treatment of alcohol and nicotine in dually-dependent patients. Finally, the proposed study will continue and extend the scope of our ongoing research program designed to evaluate the joint effects of behavioral and pharmacological interventions for substance dependence.